Intraocular Cell Migration Inhibition System

ABSTRACT

Generally, an intraocular implant and methods for treating an ocular condition. In particular, an intraocular implant which implanted between an intraocular lens and the surface of the posterior capsule of the eye inhibits migration of residual lens epithelial cells after cataract surgery by providing structural barriers to reduce posterior capsule opacification of the eye.

CROSS REFERENCE TO RELATED APPLICATIONS

This U.S. patent application is a Divisional of U.S. patent applicationSer. No. 14/961,734, filed Dec. 7, 2015, which is a continuation of U.S.patent application Ser. No. 13/944, 817, filed Jul. 17, 2013, which is acontinuation of U.S. patent application Ser. No. 13/479,178, filed May23, 2012, which is a continuation-in-part of U.S. patent applicationSer. No. 13/136,515, filed Aug. 2, 2011, which is a continuation-in-partof U.S. patent application Ser. No. 12/998,652, filed May 13, 2011,which is a United States National Stage of International PatentCooperation Treaty Patent Application No. PCT/US2009/006195, filed Nov.19, 2009, which claims the benefit of U.S. Provisional PatentApplication 61/270,567, filed Jul. 10, 2009 and U.S. Provisional PatentApplication No. 61/199,674, filed Nov. 20, 2008, each herebyincorporated by reference herein.

TECHNICAL FIELD

Generally, an intraocular implant and methods for treating an ocularcondition. In particular, an intraocular implant which implanted betweenan intraocular lens and the surface of the posterior capsule of the eyeinhibits migration of residual lens epithelial cells after cataractsurgery by providing structural barriers to reduce posterior capsuleopacification of the eye.

BACKGROUND

Visually impairing cataract is the leading cause of preventableblindness in the world. Presently, the only known treatment for cataractis the surgical removal of the opacified lens of the affected eye andreplacement with an artificial intraocular lens, typically including anintraocular lens optic and haptics (“IOL”). Technological advances incataract surgery with IOL implantation have made cataract surgery amongthe most effective surgical procedures.

Now referring primarily to FIGS. 1 and 2, which show a top view and across section view of a phakic eye (1). The most common technique ofcataract surgery may be extracapsular cataract extraction (“ECCE”) whichinvolves the creation of an incision (42) near the outer edge of thecornea (2) and a circular opening (44)(shown in FIGS. 3 and 4) in theanterior lens capsule (43)(also herein referred to as the “anteriorcapsule”) through which the opacified lens (3) can be removed from thelens capsule (45)(also referred to as the “capsular bag”). Now referringprimarily to FIGS. 3 and 4 which show a top view and a cross sectionview of a pseudophakic eye (4), the lens capsule (45) anchored to theciliary body (6) through the zonular fibers (7) can be leftsubstantially intact. The IOL (8) can then be placed within the lenscapsule (45) through the circular opening (44) in the anterior capsule(43). The IOL (8) can be acted on by zonular forces exerted on the outercircumference of the lens capsule (45) which establishes the location ofthe IOL (8) within the lens capsule (45). The intact posterior capsule(5) acts as a barrier to the vitreous humor (9) within the posteriorsegment of the eye.

The most frequent complication to ECCE and other methods of cataractsurgery can be opacification of the posterior capsule (5). Posteriorcapsule opacification (“PCO”) results from the migration of residuallens epithelial cells (“LEC”) between the IOL (8) and the surface of theposterior capsule (5) subsequent to cataract surgery. The residual LECsonce located between the IOL (8) and the surface of the posteriorcapsule (5) can proliferate leading to clouding of the normally clearposterior capsule (5). Clouding of the posterior capsule (5) candecrease visual acuity if the opacification occurs within the visualaxis (21).

Visually significant PCO requires an additional surgery to clear thevisual axis of the eye. Presently, the most widely utilized procedure toclear the visual axis of PCO may be Neodymium: Yttrium-Aluminum-Garnet(“Nd:YAG”) laser capsulotomy. However, there may be substantial problemswith this procedure such as IOL damage, postoperative intraocularpressure spikes, vitreous floaters, cystoid macular edema, retinaldetachment, and IOL subluxation, or the like. Additionally, pediatricpatients can be difficult to treat and a delay in treatment can lead toirreversible amblyopia. Many underdeveloped countries do not have accessto a Nd:YAG laser and the cost can be prohibitive.

Prevention or inhibition of PCO fall into two broad categories:mechanical and pharmacological. Mechanical mechanisms to inhibit PCOhave primarily focused on configuration of the IOL (8). Configuring theIOL to include a sharp posterior edge may provide a structural barrierto the migration of residual LECs between the IOL and the surface of theposterior capsule (5). Cleary et al., Effect of Square-edged IntraocularLenses on Neodymium: YAG Laser Capsulotomy Rates in the United States,J. Cataract & Refractive Surgery, Vol. 33, p. 1899-1906 (November 2007).However, while introduction of square edged IOLs appears to have reducedincidence of PCO, a review of Medicare claims data from 1993 to 2003evidences that the number of laser capsulotomies performed in the UnitedStates to treat PCO in recipients of square edged IOL remainssubstantial.

Pharmacological mechanisms have been proposed as a way to inhibit orprevent PCO. The effect of topical treatment with nonsteroidalanti-inflammatory drugs (“NSAIDs”) such as diclofenac and indomethacinafter phacoemulsification do not appear to inhibit PCO. Inan et al.,Effect of Diclofenac on Prevention of Posterior Capsule Opacification inHuman Eyes, Can J Ophthalmol, 41; 624-629 (2006). Additionally, themajority of pharmacological agents tested in-vitro for inhibition ofmigration and proliferation of LECs are antimetabolites and antimitoticswhich have not been used clinically because of their toxic side effects.Inan U U, Ozturk F, Kaynak S, et al. Prevention of Posterior CapsuleOpacification by Intraoperative Single-dose Pharmacologic Agents, JCataract Refract Surg, 27:1079-87(2001); Inan U U, Ozturk F, Kaynak S.Ilker S S, Ozer E, Güler, Prevention of Posterior Capsule Opacificationby Retinoic Acid and Mitomycin, Graefes Arch Clin Exp Ophthalmol 239:693-7(2001); Cortina P, Gomez-Lechon M J, Navea A, Menezo J L, TerencioM C, Diaz-Llopis, M, Diclofenac Sodium and Cyclosporine A Inhibit HumanLens Epithelial Cell Proliferation in Culture, Graefes Arch Clin ExpOphthalmol 235: 180-5(1997); Ismail M M, Alio J L, Ruiz Moreno J M,Prevention of Secondary Cataract by Antimitotic Drugs: ExperimentalStudy, Ophthalmic Res, 28:64-9 (1996); Emery J., Capsular OpacificationAfter Cataract Surgery, Curr Opin Ophthalmol, 10:73-80 (1999); HartmannC, Wiedemann P, Gothe K, Weller M, Heimann K, Prevention of SecondaryCataract by Intracapsular Administration of the Antibiotic Daunomycin,Ophthalmologic, 4:102-6 (1990).

Also, available is a sealed capsule irrigation device which functions toallow selective irrigation of the lens capsule with LEC inhibitingpharmacologic agents. Maloof A J, Neilson G, Milverton E J, Pandy S K,Selective and specific targeting of lens epithelial cells duringcataract surgery using sealed-capsule irrigation, J Cataract RefractSurg, 29:1566-68 (2003). It is not clear, however, that use of thedevice can be reduced to routine practice.

Problems relating to incomplete seal of the lens capsule (45) resultingin leakage of potentially toxic chemicals into the anterior chamber (46)of the eye, rupture of the lens capsule (45) during manipulation of theirrigation device, difficulty in assessing kill of LECs within the lenscapsule (45) and an increase in the duration of routine cataract surgerylimit the usefulness of the irrigation device.

Another prominent problem with routine cataract surgery and othersurgical procedures such as retinal surgery, cornea transplant surgery,glaucoma surgery, or the like, can be postoperative administration ofantibiotics to prevent endophthalmitis. Topical antibiotic andanti-inflammatory eye drops represent the mainstay of drug delivery forintraocular surgery. However, there has yet to be a prospectiverandomized study showing that topical antibiotics preventendophthalmitis. Also, because the human cornea acts as a naturalbarrier to biologic and chemical insults, intraocular bioavailabilityusually requires frequent dosing regimens for each medication. Topicaldrops can be difficult for young and elderly patients and the dropschedule can be cumbersome and confusing particularly when followingsurgery each eye is on a different drop schedule. These difficulties canresult in non-compliance with serious consequences such asendophthalmitis, glaucoma, and cystoid macular edema. Recent prospectivestudies supporting the use of intracameral antibiotic injections forprophylaxis of endophthalmitis have stirred debate regarding the risksassociated with this method of antibiotic prophylaxis including theshort duration of protective effect (possibly less than 24 hours), theintroduction of potentially contaminated substances in the anteriorchamber, endothelial cell toxicity, toxic anterior segment syndrome,dilutional and osmolarity errors during mixing, and the like. Also, thesystemic administration of drugs for treatment of localized ocularconditions may not be preferred because of the inefficiency associatedwith indirect delivery of the drugs to a target organ.

Recognizing these disadvantages of conventional delivery of antibioticsand other drugs to the eye, external ocular inserts were developedutilizing biologically inert materials to act as a reservoir for slowrelease of the drug. These external ocular inserts may be placed withinthe upper and lower conjunctival fornix of the eye to achieve a uniformsustained rate of release of drug in therapeutically effective amounts.However, patients can be intolerant of these devices due to difficultyin insertion and removal and mild to moderate conjunctival irritationduring use which may explain why external ocular inserts have not beenwidely accepted in clinical practice.

DISCLOSURE OF INVENTION

Accordingly, a broad object of the invention can be to provide anintraocular implant having patterned surface elements which implantedbetween an intraocular lens and the surface of the posterior capsule ofthe eye provides a mechanical barrier which inhibits migration ofresidual lens epithelial cells after cataract surgery for treatment ofan ocular condition.

Another broad object of the invention can be to provide a biocompatibleintraocular implant and methods of treatment of an ocular condition byimplantation of the biocompatible intraocular implant inside the eyewith embodiments which can be intraocularly implanted in the posteriorcapsule of the eye to provide pharmaceutical barriers to interruptprogression of the ocular condition, the ciliary sulcus between the irisand the lens, or in the anterior chamber overlaying the iris.

Another broad object of the invention can be to provide a biocompatibleintraocular implant locatable between the surface of the posteriorcapsule of the eye and an implanted IOL to provide a mechanical barrierwhich inhibits migration of residual lens epithelial cells aftercataract surgery by providing structural barriers to reduce posteriorcapsule opacification of the eye.

Another broad object of the invention can be to provide a biocompatiblebiodegradable intraocular implant locatable between the surface of theposterior capsule of the eye and an implanted IOL to provide abiodegradable mechanical barrier for treatment of an ocular condition.

Another broad object of the invention can be to provide a biocompatiblebiodegradable intraocular implant locatable between the surface of theposterior capsule of the eye and an implanted IOL which combines abiocompatible biodegradable material which continually, or substantiallycontinually, releases a therapeutically effective amount of an activeagent to treat an ocular condition.

Another broad object of the invention can be to provide a biocompatiblebiodegradable intraocular implant locatable between the surface of theposterior capsule of the eye and an implanted IOL during cataractsurgery which by structural or pharmaceutical barriers inhibitsmigration of residual lens epithelial cells to the surface of theposterior capsule.

Another broad object of the invention can be to provide a biocompatiblebiodegradable intraocular implant locatable between the surface of theposterior capsule of the eye and an implanted IOL during cataractsurgery which by structural or pharmaceutical barriers inhibitsproliferation of residual lens epithelial cells to the surface of theposterior capsule as a prophylaxis of PCO.

Another broad object of the invention can be to provide a biocompatibleor biocompatible biodegradable intraocular implant locatable anterior tothe natural crystalline lens or an implanted IOL within the ciliarysulcus for administration of one or more active agents.

Another broad object of the invention can be to provide a biocompatibleor biocompatible biodegradable intraocular implant locatable in theanterior chamber overlaying the iris.

Naturally, further objects of the invention are disclosed throughoutother areas of the specification, drawings, photographs, and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top view of the phakic eye with the natural lens intact.

FIG. 2 is a cross section 2-2 of the phakic eye with the natural lensintact.

FIG. 3 is a top view of the pseudophakic eye having the natural lensreplaced with an IOL.

FIG. 4 is a cross section 4-4 of the pseudophakic eye having the naturallens replaced with an IOL.

FIG. 5 is a front view of a particular embodiment of the inventiveintraocular implant of generally circular configuration.

FIG. 6 is a front view of a particular embodiment of the inventiveintraocular implant of generally circular configuration which terminatesradially in an annular member.

FIG. 7 is a back view of a particular embodiment of the inventiveintraocular implant further providing patterned surface elements.

FIG. 8 is enlarged partial back view of the particular embodiment of theinventive intraocular implant shown in FIG. 6 providing patternedsurface elements.

FIG. 9 is a perspective view of the particular embodiment of theinventive intraocular implant shown in FIG. 5.

FIG. 10 is a cross section view 10-10 of the particular embodiment ofthe inventive implant shown in FIG. 9.

FIG. 11 is a cross section view 11-11 of the particular embodiment ofthe inventive implant shown in FIG. 6.

FIG. 12 is a perspective view of a particular embodiment of theinventive intraocular implant.

FIG. 13 is a cross section view 13-13 of the particular embodiment ofthe inventive implant shown in FIG. 12.

FIG. 14 is plan view of a particular embodiment of the inventiveintraocular implant.

FIG. 15 is a cross section view 15-15 of the particular embodiment ofthe inventive implant shown in FIG. 14.

FIG. 16 is a side view of the particular embodiment of the inventiveimplant shown in FIG. 14.

FIG. 17 is a front view of a particular embodiment of the inventiveintraocular implant which further provides radial slit elementsoriginating at the outer boundary.

FIG. 18 is a front view of a particular embodiment of the inventiveintraocular implant which further provides radial slit elementsoriginating at the aperture element.

FIG. 19 is a front view of a particular embodiment of the inventiveintraocular implant which further provides perforation elements.

FIG. 20 is a front view of a particular embodiment of the inventiveintraocular implant which further provides two more flexible membranezones.

FIG. 21 is an enlarged partial back view of the particular embodiment ofthe inventive intraocular implant shown in FIG. 6 which shows aparticular embodiment of patterned surface elements in the form of aplurality of raised elements.

FIG. 22 is cross section 22-22 of the patterned surface elements shownin FIG. 21.

FIG. 23 is an enlarged partial back view of the particular embodiment ofthe inventive intraocular implant in FIG. 6 which shows a particularembodiment of the patterned surface elements in the form of a pluralityof recessed elements.

FIG. 24 is cross section 24-24 of the patterned surface elements shownin FIG. 23.

FIG. 25 is an enlarged partial back view of the particular embodiment ofthe inventive intraocular implant in FIG. 6 which shows a particularembodiment of the patterned surface elements in the form of a pluralityof raised elements on the back surface and a plurality of recessedelements on the front surface.

FIG. 26 is cross section 26-26 of the patterned surface elements shownin FIG. 25 which shows a plurality of raised elements on the backsurface of a particular embodiment of the inventive intraocular implantand a plurality of recessed elements on the front surface of theinventive intraocular implant.

FIG. 27 is an enlarged partial front view of the particular embodimentof the inventive intraocular implant shown in FIG. 6 which shows anotherparticular embodiment of the patterned surface elements.

FIG. 28 is cross section 28-28 of the patterned surface elements shownin FIG. 27.

FIG. 29 is an enlarged partial front view of the particular embodimentof the inventive intraocular implant shown in FIG. 6 which shows anotherparticular embodiment of the patterned surface elements.

FIG. 30 is cross section 30-30 of the patterned surface elements shownin FIG. 29.

FIG. 31 is an enlarged partial front view of the particular embodimentof the inventive intraocular implant shown in FIG. 6 which shows anotherparticular embodiment of the patterned surface elements.

FIG. 32 is cross section 32-32 of the patterned surface elements shownin FIG. 31.

FIG. 33 is an enlarged partial front view of the particular embodimentof the inventive intraocular implant shown in FIG. 6 which shows anotherparticular embodiment of the patterned surface elements.

FIG. 34 is cross section 34-34 of the patterned surface elements shownin FIG. 33.

FIG. 35 is a front view of a particular embodiment of the inventiveintraocular implant which further provides one or more boundary recesselements.

FIG. 36 is a front view of a particular embodiment of the inventiveintraocular implant which includes both radial slit elements originatingfrom the aperture element and boundary recess elements whichperiodically interrupt the outer boundary.

FIG. 37 is a perspective view of a plurality of an embodiment of theinventive intraocular implant which can be stacked front to back.

FIG. 38 is a perspective view of an embodiment of the inventiveintraocular implant which further provides radial capillary elements.

FIG. 39 is a perspective view of an embodiment of the inventiveintraocular implant which further provides corrugate elements.

FIG. 40 shows an embodiment of the intraocular implant held by forcepsfor implantation into an eye having the natural lens removed.

FIG. 41 is top view of the pseudophakic eye having the natural lensremoved allowing an embodiment of the intraocular implant to bepositioned on the surface the posterior capsule through an opening madein the anterior capsule.

FIG. 42 is a cross section view of the pseudophakic eye having thenatural lens removed allowing an embodiment of the intraocular implantto be positioned on the surface the posterior capsule through anincision made in the anterior capsule.

FIG. 43 is a cross section view of the pseudophakic eye having theintraocular implant of FIG. 9 positioned between the surface theposterior capsule and the implanted IOL.

FIG. 44 is a cross section view of the pseudophakic eye having theintraocular implant of FIG. 6 positioned between the surface theposterior capsule and the implanted IOL.

FIG. 45 is a cross section view of the pseudophakic eye having theintraocular implant of FIG. 12 positioned on the surface of theposterior capsule.

FIG. 46 is a cross section view of the phakic eye having the intraocularimplant of FIG. 9 positioned between the iris and the naturalcrystalline lens of the eye.

FIG. 47 is front view of an embodiment of the intraocular implantaffixed to a sterile card prior to implantation.

FIG. 48 is a side view of an embodiment of the intraocular implantaffixed to a sterile card prior to implantation.

MODE(S) FOR CARRYING OUT THE INVENTION

Generally, an intraocular implant and methods for treating an ocularcondition. In particular, an intraocular implant which implanted betweenan intraocular lens and the surface of the posterior capsule of the eyeinhibits migration of residual lens epithelial cells after cataractsurgery by providing structural barriers to reduce posterior capsuleopacification of the eye.

Definitions

“A” or “an” entity refers to one or more of that entity; for example, “apolymer” refers to one or more of those compositions or at least onecomposition. As such, the terms “a” or “an”, “one or more” and “at leastone” can be used interchangeably herein. Furthermore, the language“selected from the group consisting of” refers to one or more of theelements in the list that follows, including combinations of two or moreof the elements.

“About” for the purposes of the present invention means that ranges maybe expressed as from “about” one particular value to “about” anotherparticular value. When such a range is expressed, another embodimentincludes from the one particular value to the other particular value.Similarly, when values are expressed as approximations, by use of theantecedent “about,” it will be understood that the particular valueforms another embodiment. In the context of such a numerical value orrange “about” means plus or minus 10% of the numerical value or rangerecited or claimed.

“Active agent” for the purposes of this invention means any substanceused to treat an ocular condition.

“Biocompatible” for the purposes of this invention means the ability ofany material to perform the intended function of an embodiment of theinvention without eliciting any undesirable local or systemic effects onthe recipient and can include non-biodegradable materials such as:polyurethanes, polyisobutylene, ethylene-alpha-olefin copolymers,acrylic polymers and copolymers, vinyl halide polymers and copolymers,polyvinyl esters, polyvinylidene chloride, polyacrylonitrile, polyvinylketones, polyvinyl aromatics such as polystyrene, copolymers of vinylmonomers and olefins such as ethylene-methyl methacrylate copolymers,acrylonitrile-styrene copolymers, ABS resins, ethylene-vinyl acetatecopolymers, polyamides such as Nylon 66 and polycaprolactone, alkydresins, polycarbonates, polyoxyethylenes, polyimides, polyesters, epoxyresins, rayon-triacetate, cellophane, silicon rubber, silicon hydrogel,or the like, or biodegradable materials, as herein described.

“Biodegradable” for the purposes of this invention means the ability ofany biocompatible material to breakdown within the physiologicalenvironment of the eye by one or more physical, chemical, or cellularprocesses at a rate consistent with providing structural orpharmaceutical barriers (or both) at a therapeutic level controllable byselection of a polymer or mixture of polymers (also referred to aspolymeric materials), including, but not limited to: polylactidepolymers (PLA), copolymers of lactic and glycolic acids (PLGA),polylactic acid-polyethylene oxide copolymers,poly(c-caprolactone-co-L-lactic acid (PCL-LA), glycine/PLA copolymers,PLA copolymers involving polyethylene oxides (PEO), acetylated polyvinylalcohol (PVA)/polycaprolactone copolymers,hydroxybutyrate-hydroxyvalerate copolymers, polyesters such as, but notlimited to, aspartic acid and different aliphatic diols, poly(alkylenetartrates) and their copolymers with polyurethanes, polyglutamates withvarious ester contents and with chemically or enzymatically degradablebonds, other biodegradable nonpeptidic polyamides, amino acid polymers,polyanhydride drug carriers such as, but not limited to, poly(sebacicacid) (PSA), aliphatic-aromatic homopolymers, andpoly(anhydride-co-imides), poly(phosphoesters) by matrix or pendantdelivery systems, poly(phosphazenes), poly(iminocarbonate), crosslinkedpoly(ortho ester), hydroxylated polyester-urethanes, or the like.Hydrogels such as methylcellulose which act to release drug throughpolymer swelling are specifically excluded from the term.

“Intraocular” for the purposes of this invention means inside theeyeball (also referred to as an “eye”) and without limitation to theforgoing the anterior chamber, the ciliary sulcus, and posterior capsuleof the eye; however, specifically excluding the external surface of theeye or intracorneal or intrasclera regions of the eye.

“Localized Region” for the purposes of this invention meanssubstantially within a localized tissue region of the eyetherapeutically affected (whether structurally or pharmaceutically) byimplantation of embodiments of an intraocular implant.

“Ocular condition” for the purposes of this invention means a disease,ailment or condition which affects or involves the eye or any one of theparts or regions of the eye, such as PCO. The eye includes the eyeballand the tissues and fluids which constitute the eyeball, the periocularmuscles (such as the oblique and rectus muscles) and the portion of theoptic nerve which is within or adjacent to the eyeball.

“Posterior ocular condition” for the purposes of this invention means adisease, ailment or condition which affects or involves a posteriorocular region or site such as the choroid or sclera (in a positionposterior to a plane through the posterior wall of the lens capsule),vitreous, vitreous chamber, retina, optic nerve (i.e. the optic disc),and blood vessels and nerve which vascularize or innervate a posteriorocular region or site.

“Suitable for implantation” for the purposes of this invention meanswith regard to embodiments of the intraocular implant dimensions whichallow insertion or implantation without causing excessive tissue damage.

“Therapeutic level” for the purposes of this invention means an amountor a concentration of an active agent that has been locally delivered toan ocular region that is appropriate to reduce, inhibit, or prevent asymptom of an ocular condition.

Now generally referring to FIGS. 5-39, particular embodiments of theinventive intraocular implant (11) can provide a biocompatible flexiblemembrane or a biocompatible biodegradable flexible membrane (alsogenerally referred to as a “flexible membrane” (12)) having an outerboundary (13) configured to allow the intraocular implant (11) to locatein the concavity of the posterior capsule (5) of the pseudophakic eye(4), or other localized region inside the eye such as the ciliary sulcusor anterior chamber (46) depending on the application. As a non-limitingexample, the intraocular implant (11) can be located in the posteriorcapsule (5) for the purpose of isolating the surface of the posteriorcapsule (5) from migration of residual LECs after cataract surgery, orreducing or preventing the migration of residual LECs between thesurface of an IOL (8) implanted in the lens capsule (45) and the surfaceof the posterior capsule (5).

Intraocular implants (11) suitable for implantation can provide aflexible membrane (12) having an outer boundary (13) which as anon-limiting example defines a circular area having a diameter in arange of about 9 millimeters (“mm”) and about 15 mm depending on therecipient; however, the invention is not so limited, and the outerboundary (13) can define a substantially circular, ovoid, or otherconfiguration of the outer boundary (13) suitable for implantation intothe concavity of the posterior capsule (5) of the pseudophakic eye (4),or other localized region inside the eye.

Now referring primarily to FIG. 17, particular embodiments of theflexible membrane (12) can further include one or more radial slitelements (14) cut through the thickness of the flexible membrane withthe radial slit elements (14) originating at the outer boundary (13) cuta distance radially toward the center of the flexible membrane (12). Theone or more radial slit elements (14) can have sufficient length andwidth to allow the flexible membrane (12) to conform to a greater extentwith the concavity of the posterior capsule (5) of the pseudophakic eye(4) or other localized region inside the eye. As one non-limitingexample, the radial slit elements (14) can provide an opening in theflexible membrane (12) having a greater slit width (15) at the outerboundary (13) of the flexible membrane (12) than proximate the center ofthe flexible membrane (12). As a non-limiting example, the flexiblemembrane (12) when received by the concavity of the posterior capsule(5) can deform to reduce the slit width (15) at the outer boundary (13)of the flexible membrane (12).

Now referring primarily to FIGS. 35 and 36, particular embodiments ofthe flexible membrane can further provide one or more boundary recesselements (16) located along the outer boundary (13) of the flexiblemembrane (12). The outer boundary (13) of the flexible membrane (12) canbe interrupted once or periodically to provide one or more of the recesselements (16) which can be configured, for example, as semicircularnotches, triangular notches, indents, or the like which can function toallow added flexure to more readily locate the flexible membrane in theposterior capsule of the eye (or other localized region), as abovedescribed, or can function to reduce sequestration of peripheralcortical material during the final irrigation and aspiration steps incataract surgery.

With respect to the particular embodiments of the intraocular implantshown in FIGS. 5-39 and in particular referring to FIGS. 5, 9, and 10 asa non-limiting example, the flexible membrane (12) can have a thickness(17) disposed between a front surface (18) and a back surface (19)(alsoreferred to as “a first side” and “a second side” or “opposed sides”).As to particular embodiments of the intraocular implant (11), the frontsurface (18) and the back surface (19) can be disposed in substantiallyparallel opposed relation providing a relatively uniform thickness ofthe intraocular implant (11) in a range of about 5 microns (“μm”) andabout 400 μm, as shown by the non-limiting cross section shown in thenon-limiting example of FIG. 9. Particular embodiments of theintraocular implant, can have a uniform thickness (17) in a rangeselected from the group including: about 5 μm and about 100 μm, about 50μm and about 150 μm, about 100 μm and about 200 μm, about 150 μm andabout 250 μm, about 200 μm and about 300 μm, about 250 μm and 300 μm,300 μm and about 400 μm, and about 350 μm and about 400 μm. As toparticular embodiments, the edge (80) at the outer boundary (13) of theintraocular implant (11) can be configured to intersect each of thefront surface (18) and the back surface (19) at substantially rightangles as shown in FIG. 9. Depending upon the thickness (17) of theintraocular implant (11), the optical power of the IOL (8) can beadjusted if necessary. However, embodiments of the intraocular implantare not limited to having a uniform thickness (17) and certainembodiments of the intraocular implant (11) can provide a flexiblemembrane (12) thinner proximate the center and thicker proximate theouter boundary (13) or can provide a flexible membrane thicker proximatethe center and thinner at the edges depending upon the application. Asanother non-limiting example, the thickness (17) of the flexiblemembrane (12) may be thinner in the center to align with the visual axisof the pseudophakic eye (4) to increase visual acuity or promotedirectional biodegradation of the intraocular implant (11) from thecenter toward the outer boundary (13).

Now referring primarily to FIGS. 6, 10, 11, 12, and 13 as non-limitingexamples, the intraocular implant can further include, an annular member(74) joined about, or to the front surface (18), of the intraocularimplant (11). The surface of the edge (80) of the annular member (74)can define the outer boundary (13) of the intraocular implant (11). Theoutside surface of the edge (80) can intersect the back surface (19) ofthe flexible membrane (12) at an angle (78) which upon contact with thesurface of the posterior capsule (5) can provide a barrier or impedemigration of LECs toward the center of the intraocular implant (11).While the angle of the intersection (78) of the outside surface of theedge (80) with the back surface (19) of the intraocular implant (11) canbe substantially a right angle; the invention is not so limited, andembodiments with an angle of intersection between the outside surface ofthe edge (80) with the back surface (19) of between about 90 degrees andabout 120 degrees but retains a sharp corner can be suitable.

As to particular embodiments which include the annular member (74), theedge (80) can have a height (75) substantially greater than thethickness (17) of the flexible membrane (12). The height (75) of theedge (80) can be within the range of about 10 μm and about 1500 μmdepending upon the application. As anon-limiting example, the thickness(17) of the flexible membrane (12) can be in the range of about 50 μmand about 300 μm while the annular member (74) can provide an edge (80)having a height (75) in the range of about 300 μm and about 1500 μm;however, the invention is not so limited, and the height (75) of theedge (80) as to particular embodiments can fall outside of the rangedepending on the application.

Now referring primarily to FIG. 44 the height (75) of the edge (80) ofhe annular member (74) can be sufficiently greater than the thickness(17) of the flexible membrane (12) to provide an inside surface (77) ofthe annular member (74) having sufficient height (79) to engage thehaptics (10) of the IOL (8) engaged with the front surface (18) of theintraocular implant (11).

Now referring primarily to FIGS. 12, 13 and 45, while embodiments of theinventive intraocular implant (11) shown in FIGS. 5 through 7, 17through 20, 35 through 39 and 43 and 44 can be separate from the IOL(8); the invention is not so limited, and particular embodiments of theintraocular implant can be joined, coupled, or otherwise made one piecewith the IOL (8), or elements of the intraocular implant (11) (such asthe patterned surface elements) can be incorporated into IOL (8) suchthat the IOL (8) and those incorporated elements can be provided as aone piece IOL (8). The particular embodiment shown in FIGS. 12 and 13,shows the IOL (8), the flexible membrane (12) and the annular member(74) formed as one piece (the haptics (10) being omitted from theembodiment). The flexible membrane (12) can be joined about thecircumference of the IOL. The flexible membrane (12) can radially extendoutwardly to terminate in the edge (80) of the annular member (74). Thedimensional relations of the flexible member (12) and the annular member(74) can be as above-described. A plurality of radial struts (81) can becoupled to the front surface (18) of the intraocular implant (11)between the circumference of the IOL (8) and the inside surface (77) ofthe annular member (74) having dimensional relations sufficient tomaintain the front surface (18) and the back surface (19) of theflexible membrane (12) and the annular member (74) in proper relation tothe a pseudophakic eye (4) upon implantation as shown in thenon-limiting example of FIG. 42. Accordingly, the surgical techniquedescribed below can include the steps of implanting into the lenscapsule (45) the IOL (8) joined, coupled or otherwise made one piecewith to the intraocular implant (11) or elements thereof.

Now referring primarily to FIGS. 6 through 8, FIGS. 12 through 16, andFIGS. 21 through 34, particular embodiments of the intraocular implant(11), can provide patterned surface elements (20) coupled to the backsurface (19) of the intraocular implant (11). The patterned surfaceelements (20) can be adapted to engage the surface of the posteriorcapsule (5) to reduce travel of the intraocular implant (11) or maintainthe alignment of the center of the intraocular implant (11) with thevisual axis of the eye (21). The patterned surface elements (20) canprovide an irregular or uniform pattern, texture, or roughnesssufficient to fix or reduce travel of the intraocular implant (11) inthe posterior capsule (5).

As to certain embodiments of the intraocular implant (11) the patternedsurface elements (20) can also provide pockets which function to providea localized space to deliver or sequester an amount of an active agent(24). The patterned surface elements can be variously configured todeliver or sequester an active agent (24) depending on the application.The pattern surface elements (20) can be one piece with the flexiblemembrane (12) or can be applied to the flexible membrane (12) as apattern surface element layer.

As to certain embodiments of the intraocular implant (11), whether inthe form of the inventive implant as shown in the examples of FIGS. 5through 11 which can be combined with otherwise made one piece with theIOL (8) or in the form of the various embodiments of a one-piece IOL (8)as shown in the examples of FIGS. 12 through 16, patterned surfaceelements (20) can be coupled to the front surface (18) or the backsurface (19) of the intraocular implant (11) to provide an irregular oruniform pattern, texture, roughness, or dimensional relations sufficientto inhibit migration of cells, such as residual lens epithelial cells,after cataract surgery by providing structural barriers as shown in theexamples of FIGS. 21 through 34. The patterned surface elements (20) canbe configured to provide a sufficient structural barrier to themigration of residual lens epithelial cells to eliminate, substantiallyeliminate or reduce posterior capsule (5) opacification of thepseudophakic eye (4). As to certain embodiments, the intraocular implant(11) can include the IOL (8) comprising an intraocular lens optic (82)and an intraocular lens haptic (83) with patterned surface elements (20)coupled to at least a part of said IOL (8) while maintaining a line ofsight (21) through the intraocular lens optic (82), the patternedsurface elements (20) having dimensional relations adapted to inhibitmigration of cells between the IOL (8) and the surface of said posteriorcapsule (5) of the eye.

In general, the patterned surface elements (20) can include a pluralityof raised elements (47) or a plurality of recessed elements (69) whichproject outwardly or recess inwardly from the back surface (19) or thefront surface (18) of the biocompatible flexible membrane (12) of theintraocular implant (11) in spaced apart relation to one another.

As to certain embodiments, the plurality of raised elements (47) can bebounded by a corresponding plurality of channels (48) which form apattern over the entirety or over a portion of the back surface (19) orthe front surface (18), or both the front surface (18) and the backsurface (19) of the biocompatible flexible membrane (12) of theintraocular implant (11). The plurality of raised elements (47) can beproduced from one or more of the biocompatible or biodegradablematerials, as above described, which as to certain embodiments can be amaterial different than used to form the biocompatible or biocompatiblebiodegradable flexible membrane (12). The top surface (49) of each ofthe plurality of raised elements (47) can be generally flat or planarhaving a surface area sufficiently small to reduce or prevent adhesionor migration of residual lens epithelial cells across the plurality ofraised elements (47) and each of the plurality of channels (48) can besufficiently small to reduce or prevent migration or adhesion betweenthe plurality of raised elements (47). The plurality of raised elements(47) can be disposed in spaced apart relation on the back surface (19)or the front surface (18), or both, of the biocompatible orbiocompatible biodegradable flexible membrane (12) to dispose theplurality of channels in a non-linear path (67) inwardly approaching thecenter of the intraocular implant (11). The various embodiments of thepatterned surface elements (20) can occur only on the back surface (19),only on the front surface (18) or can occur on both the back surface(19) and on the front surface (18).

Embodiments of the top surface (49) of each of the plurality of raisedelements can have a lesser dimension between two sidewalls (50)(see forexample FIG. 13) in the range of about 500 nanometers and about 4micrometers. Depending upon the application, the lesser dimension can beselected from the group including: about 400 nanometers and about 1micrometer, about 500 nanometers and about 1.5 micrometers, 1 micrometeran about 2.0 micrometers, 1.5 micrometers and about 2.5 micrometers, 2.0micrometers and about 3.0 micrometers, 2.5 micrometers and about 3.5micrometers, 3.0 micrometers and about 4.0 micrometers, and 3.5micrometers and about 4.0 micrometers, or combinations thereof.

Understandably, the top surface (49) as between two or more of theplurality of raised elements (47) can be configured in substantiallysimilar configuration and similar in dimensional relations or as betweentwo or more of the plurality of raised elements (47) can besubstantially different in configuration or irregular in dimensionalrelations. The lesser dimension can as to particular embodiments relateto the width of one of the plurality of raised elements (47) and thegreater dimension as to particular embodiments can relate to a length ofone of the plurality of raised elements (47). However, the invention isnot so limited; and numerous and varied embodiments can be produced inwhich the top surface has an irregular surface area, or may besubstantially circular or can be a regular polygon, or the like, whichdo not afford a distinction between width and length. Accordingly, theabove dimensions afford guidance sufficient for the person of ordinaryskill in the art to provide a plurality of raised elements (49) inspaced apart relation having a wide variety of configurations useful ininhibiting adhesion and migration of cells toward the center of theintraocular implant (11).

The sidewalls (50) of each of the plurality of raised elements (47) canbe generally vertical to the surface of the intraocular implant (11)when the biocompatible flexible membrane (12) is disposed in a generallyflat condition. The sidewalls (50) can have a sidewall height (51) inthe range of about 400 nanometers and about 6 micrometers. Dependingupon the application, the sidewall height (51) can be selected from thegroup including: about 400 nanometers and about 1 micrometer, about 500nanometers and about 1.5 micrometers, 1 micrometer an about 2.0micrometers, 1.5 micrometers and about 2.5 micrometers, 2.0 micrometersand about 3.0 micrometers, 2.5 micrometers and about 3.5 micrometers,3.0 micrometers and about 4.0 micrometers, 3.5 micrometers and about 4.5micrometers, 4.0 micrometers and about 5.0 micrometers, about 4.5micrometers and about 5.5 micrometers, and about 5.0 micrometers andabout 6.0 micrometers, or combinations thereof.

Each of the plurality of channels (48) defined by opposed sidewalls (50)can have a channel width (61) in the range of about 100 nanometers andabout 2.5 micrometers. Depending upon the application, a suitablechannel width (61)(see for example FIG. 17) can be selected from thegroup including: 100 nanometers and about 300 nanometers, about 200nanometers and about 400 nanometers, about 300 nanometers and about 500nanometers, about 400 nanometers and about 600 nanometers, about 500nanometers and about 700 nanometers, about 600 nanometers and about 800nanometers, about 700 nanometers and about 900 nanometers about 800nanometers and about 1 micrometer, about 900 nanometers and about 1.1micrometer, 1 micrometer an about 1.2 micrometer, 1.1 micrometer andabout 1.3 micrometer, 1.2 micrometer and about 1.4 micrometer, 1.3micrometer and about 1.5 micrometers, 1.4 micrometer and about 1.6micrometer, 1.5 micrometer and about 1.7 micrometer, 1.6 micrometer andabout 1.8 micrometer, 1.7 micrometer and about 1.9 micrometer, and about1.8 micrometer and about 2 micrometer, or combinations thereof.

Now referring primarily to FIGS. 21 through 34, which providenon-limiting examples of raised elements (20) or recessed elements (69)which can be useful in inhibiting the migration of cells between theback surface (19) of the biocompatible flexible membrane (12) and thesurface of the posterior capsule (5) of the a pseudophakic eye (4) orcan be useful in inhibiting the migration of cells between the frontsurface (18) and an implanted intraocular lens (8).

As to the non-limiting example of FIGS. 21-26, the patterned surfaceelements (20) can have the topography (or reverse topography) of ashark's skin as described in U.S. Pat. No. 7,650,848, herebyincorporated by reference herein to the extent that that the descriptiondoes not conflict with the express description of embodiments of thepatterned surface elements (20). The topography of the shark skin can bescaled to inhibit adhesion and migration of residual lens epithelialcells between the back surface (19) of the intraocular implant (11) andthe surface of the posterior capsule (5) of the pseudophakic eye (4). Asone non-limiting example, the topography of the shark skin can becharacterized by a plurality of repeating diamond patterns (52) eachconsisting of a plurality of raised elements (47) including seven barelements (53). The diamond pattern (52) can have an overall diamondlength (68) in the range of about 15 micrometers and about 25micrometers. Each of the seven bar elements (53) can have a bar width(60) in the range of about 1 micrometer and about 2.5 micrometers andhaving a corresponding one of a plurality of channels (48) each havingchannel width (61) of about 400 nanometers and about 2 micrometer. Theseven bar elements (53) can have a bar length (54) in the range of about4 micrometers and about 20 micrometers. The height of the side wall (50)for each of the seven bar elements (53) can be in the range of about 1micrometer and about 5 micrometers.

Now referring primarily to FIGS. 23-24, particular non-limiting examplesof the patterned surface elements (20) can take the form of thetopography of a shark's skin as above described; however, the pluralityof raised elements (47) and plurality of channel (48) can be replaced bya corresponding plurality of recessed elements (69) having correspondingplurality of bottom surfaces (70) and spacer elements (71) having acorresponding spacer width (73) to form substantially the same patternhaving substantially the same dimensional relations as above described.Again, any of patterned surface elements (20) described herein as aplurality of raised elements (47) and a corresponding plurality ofchannel elements (48) can take the constructional form of a plurality ofrecessed elements (70) and a plurality of spacer elements (71) havingsubstantially the same or similar pattern or dimensional relations inthe ranges above described.

Now referring primarily to FIGS. 25 and 26, particular embodiments ofthe patterned surface elements (20) can take the form of a plurality ofraised elements (47) on one side of the biocompatible flexible membrane(12) and a plurality of recessed elements (69) on the opposed side ofthe biocompatible flexible membrane (12). While FIGS. 20 and 21 show aplurality of raised elements (47) on the back side (19) of thebiocompatible flexible membrane (12) and a plurality of recessedelements (69) on the front side (18) of the biocompatible flexiblemembrane (12); the invention is not so limited, and the a plurality ofrecessed elements (69) can occur on the back side (19) while theplurality of raised elements can occur on the front side (18) of thebiocompatible flexible membrane (12).

Now referring primarily to FIGS. 27 and 28, particular embodiments ofthe patterned surface elements (20) can take the form of a plurality ofraised elements (47) each having a generally cylindrical configurationin spaced apart relation of columns and rows. Each of the plurality ofraised elements (47) having substantially circular top surface (49)having a diameter in the range of about 400 nanometers and about 600nanometers and side wall (50) having a height of about 400 nanometersand about 600 nanometers. The plurality of raised elements (47) can beestablished on centers in the range of about 600 nanometers and about 1micrometer affording a distance between the sidewalls (50) of betweenabout 200 nanometers and about 400 nanometers.

Now referring primarily to FIGS. 29 and 30, particular embodiments ofthe patterned surface elements (20) can take the form of a plurality ofraised elements (47) in the form of a plurality of repeating barpatterns (55) each characterized by four bar elements (56) ofsubstantially equal length in spaced apart generally parallel relationhaving corresponding aligned first ends (57) and aligned second ends(58) with a cross bar (59) disposed in generally perpendicular relationa distance from the aligned first ends (57) or aligned second ends (58)of the four bar elements (56). Each of the four bar elements (56) canhave a width (60) in the range of about 2 micrometers and about 5micrometers and having a corresponding one of a plurality of channels(48) each having width (61) of about 400 nanometers and about 1micrometer. The four bar elements (56) can each have a length (62) inthe range of about 4 micrometers and about 20 micrometers. The height ofthe side wall (50) of each of the four bar elements (56) can be in therange of about 1 micrometer and about 3 micrometers. The cross bar (59)can be disposed a distance from the aligned first ends (57) or alignedsecond ends (58) of the four bar elements (56) (or may alternate betweenthe aligned first ends (57) and aligned second ends (58) as the patternrepeats) in the range of about 400 nanometers and about 1 micrometer.The length of the cross bar (59) can be sufficient to span the distanceof the spaced apart relation of the four bar elements (56). The crossbar (59) having dimensional relations otherwise similar to the four barelements (56).

Now referring primarily to FIGS. 31 and 32, embodiments of the patternedsurface elements (20) can take the form of a plurality of raisedelements (47) each having a top surface (20) of generally hexagonalconfiguration in regular spaced apart tessellation. Each of thehexagonal top surface (49) can have a width (60) in the range of about400 nanometers and about 600 nanometers and side wall (50) having aheight of about 400 nanometers and about 600 nanometers. Thecorresponding plurality of channels (48) can have a width (61) of about100 nanometers and about 200 nanometers between each of the plurality ofraised elements (47).

Now referring primarily to FIGS. 33 and 34, embodiments of the patternedsurface elements (20) can take the form of a plurality of raisedelements (47) in the form of a plurality of bar elements (65) in aherringbone pattern. Each of the plurality of bar elements (65) can beof substantially equal length in the range of about 4 micrometers andabout 20 micrometers and having a width (61) in the range of about 2micrometers and about 5 micrometers. The height of the side walls (51)of each of the plurality of bar elements (65) can be in the range ofabout 1 micrometer and about 3 micrometers. The corresponding pluralityof channels (48) between the plurality of bar elements (65) can have achannel width (60) of about 400 nanometers and about 1 micrometer.

Now referring primarily to FIG. 19, certain embodiments of the flexiblemembrane (12) can further include one or more perforation elements (22)which provide a corresponding one or more perforation openings (23)which communicate between the front surface (18) and the back surface(19) of the flexible membrane (12) for the purpose of increasing rate ofbiodegradation of the flexible membrane (12) or control release rate ofan active agent (24). The active agent (24)(shown for example in FIGS.9, 10 and 13 as a stipple pattern) is not intended to be limited tothose particular embodiments of the intraocular implant (11) or limitthe active agent (24) to any particular composition, particle size, oramount.

Now referring primarily to FIG. 37, certain embodiments of the flexiblemembrane (12) can further provide two or more flexible membrane layers(25). The two or more membrane layers (25) can take the form of a firstflexible membrane layer (26) and a second flexible membrane layer (27)or additional flexible membrane layers (28) extruded as a single piece,coupled together as one unit, or stacked front to back (whether singlepiece, coupled or stacked the term “coupled” may be used to refer to theassociation of a plurality of flexible membrane layers). Each of thefirst flexible membrane layer (26) and the second flexible membranelayer (27) or additional flexible layers (28) can be generated from thesame or different biocompatible biodegradable materials. As anon-limiting example, in an embodiment of the invention for thetreatment of PCO, the first flexible membrane layer (26) can be made ofa biocompatible or biocompatible biodegradable material which can havethe back surface (19) disposed adjacent the surface of the posteriorcapsule (5) to provide both a structural barrier to the migration ofLECs to the surface of the posterior capsule but to further function asa pharmaceutical barrier which inhibits proliferation or kills LECs bythe substantially continuous release of an active agent (24) such asalkylphosphocholine at a rate which provides a therapeutic level, suchas a localized concentration of about 1.0 millimolar (“mM”) for a periodof at least five days to inhibit or prevent PCO. The front surface (18)of the first flexible membrane layer (26) can be coupled adjacent theback surface (19) of the second flexible membrane layer (27) (forexample by melt co-extrusion) produced from the same or differentbiocompatible biodegradable material and the front surface (18) of thesecond flexible membrane layer (27) can be disposed toward an IOL (8)implanted into the posterior capsule (5) to provide a structural barrierto migration of LECs toward the surface of the posterior capsule and canfurther function as a pharmaceutical barrier which inhibitsproliferation or kills LECs by the substantially continuous release ofthe same active agent (24) (such as an alkylphosphocholine) or adifferent active agent (24) such as mitomycin-C at a therapeutic level,such as a localized concentration of about 0.04 mg/mL, for a period ofat least about five days to inhibit or prevent PCO. Thus, by configuringthe layers in different combinations the rate of release of variousactive agents can be adjusted depending on the application.

Now referring primarily to FIG. 20, two or more flexible membrane zones(29) can be established with each flexible membrane zone (29) generatedfrom a particular flexible membrane material. As to certain embodiments,the two or more flexible membrane zones (29) can be established asconcentric regions with a first annular zone (30) surrounded by a secondannular zone (31). The first annular zone (30) can be of differentbiocompatible or biocompatible biodegradable material then the secondannular zone (31). For example, the first annular zone (30) can providea biocompatible biodegradable material selected for a greater rate ofbiodegradation or active agent (24) release (or both) relative to thesecond annular zone (31) which can provide a biocompatible biodegradablematerial selected for a lesser rate of biodegradation or active agent(24) release (or both). In that configuration of the inventiveintraocular implant (11), the prominent function of the first annularzone (30) can be to provide a pharmaceutical barrier or treatment of anocular disorder, while the prominent function of the second annular zone(31) can be to provide a structural barrier or treatment of an oculardisorder. In particular embodiments of the inventive intraocular implantfor the inhibition of PCO, the first annular zone can be made of thebiocompatible biodegradable material poly(lactide-co-glycolide) havingan active agent (24) such as alkylphosphocholine dispersed substantiallyuniformly through out which can provide a pharmaceutical barrier to theproliferation of LECs on the surface of the posterior capsule (5) toinhibit or prevent PCO by release of a therapeutic level ofalkylphosphocholine of about 1.0 mM for a period of at least about fivedays. The first annular zone (30) can substantially biodegrade in theentirety in a period of about five days to about ten days. The secondannular zone can be made of the same biocompatible biodegradablematerial having the same or different active agent (24) dispersedsubstantially uniformly throughout to provide both a structural barrierto inhibit migration of LECs toward to the surface of the posteriorcapsule and can provide a pharmaceutical barrier by release of the sameor different active agent (24) such as alkylphosphocholine at atherapeutic level or provide a localized concentration of about 1.0 mMfor a period of at least twenty days to inhibit or prevent PCO.

Again referring generally to FIGS. 5 through 11, 17 through 20, and 35through 36, particular embodiments of the inventive intraocular implant(11) can further include an aperture element (32) having a passageopening (33) sufficiently large to align with the visual axis of the eye(21) to provide a line of sight which passes through the intraocularimplant (11) or the first annular zone (30) or the second annular zone(31).

While the aperture element (32) shown in FIGS. 5 through 11, 17 through20, and 35 through 39 define a substantially circular passage openinghaving a diameter in the range of about 1.5 mm and about 9 mm dependingupon the application and the recipient; the invention is not so limitedand certain embodiments of the inventive intraocular implant (11) canprovide an aperture element (32) which defines an oval, square,triangle, or other configuration of passage opening (33) sufficient toprovide a line of sight which passes through the intraocular implant(11). As to those embodiments of the invention which are utilized withan intraocular optical implant, such as an IOL as further describedherein, the passage opening (33) can be dimensioned in relation to theintraocular optical implant to avoid reduction in the field of visionprovided by the intraocular optical implant or to avoid a reduction inclarity of vision within visual field. Alternately, in those embodimentsof the invention in which the passage opening (33) has insufficientdimension to avoid overlaying all or part of the visual field affordedby the intraocular optical implant, embodiments of the intraocularimplant (11) can be further configured to provide an optical element ofsufficient clarity so as not to substantially effect vision within thevisual field afforded by an intraocular implant (11).

Now referring specifically to FIGS. 18, and 36 through 38, the apertureelement (33) can further include one or more radial slit elements (14)each originating at the aperture element (33) and terminating at adistance from the outer boundary (13) of the flexible membrane (12). Theone or more radial slit elements (14) can have sufficient length andwidth to allow the flexible membrane (12) to conform to a greater extentwith the concavity of the posterior capsule (5)(or other localizedregion) of the eye and with respect to embodiments of the intraocularimplant (11) which are biodegradable can function to promote directionalbiodegradation of the intraocular implant proximate the aperture elementtoward the outer boundary (13). Again, the radial slit elements (14) canprovide one or more interruptions in the aperture element (32) which canbe of lesser or greater width or length to control the rate at which theflexible membrane (12) biodegrades within the posterior capsule (5) ofthe eye.

Now referring primarily to FIG. 38, particular embodiments of theintraocular implant (11) can further provide radial capillaries (34)which communicate between the outer boundary (13) and the apertureelement (32) of the flexible membrane (12) configured to allow orfacilitate circulation of the fluid within the eye, for example, betweenthe flexible membrane (12) and the posterior capsule (5) of the eye.

Similarly, as shown by FIG. 39, particular embodiments of theintraocular implant (11) can further provide one or more corrugateelements (35) which can be disposed in substantially linear parallelrelation to generate undulations in the flexible membrane (12)sufficient when the flexible membrane (12) locates against the surfaceof the posterior capsule (5)(or surface of a localized region) toprovide channels (36) in which the fluids of the eye can circulate.

Referring in general to FIGS. 5-39, embodiments of the intraocularimplant can further include an active agent (24)(shown as stipplepattern in FIGS. 18, 19, and 36 although the invention is not solimited) mixed with or dispersed in the biodegradable polymer of theflexible membrane (12). The composition of the biodegradable polymers ofthe flexible membrane (12) of the intraocular implant (11) can be variedto provide a continuous or substantially continuous release of atherapeutic level of a particular active agent (24) or a particularmixture of active agents (24) effective for the ocular condition beingtreated. Active agents (24) that can be used include, but are notlimited to (either alone or in combination): ace-inhibitors, endogenouscytokines, agents that influence the basement membrane, agents thatinfluence the growth of endothelial or epithelial cells, adrenergicagonists or blockers, cholinergic agonists or blockers, aldose reductaseinhibitors, analgesics, anesthetics, antiallergics, anti-inflammatoryagents, antihypertensives, pressors, antibacterials, antivirals,antifungals, antiprotozoals, anti-infectives, antitumor agents,antimetabolites such as daunomycin, antiangiogenic agents, tyrosinekinase inhibitors, antibiotics such as aminoglycosides such asgentamicin, kanamycin, neomycin, and vancomycin; amphenicols such aschloramphenicol; cephalosporins, such as cefazolin HCl; penicillins suchas ampicillin, penicillin, carbenicillin, oxycillin, methicillin;lincosamides such as lincomycin; polypeptide antibiotics such aspolymixin and bacitracin; tetracyclines such as tetracycline,minocycline, and doxycycline; quinolones such as ciprofloxacin,moxifloxacin, gatifloxacin, and levofloxacin; sulfonamides such aschloramine T; sulfones such as sulfanilic acid; anti-viral drugs such asacyclovir, gancyclovir, vidarabine, azidothymidine, dideoxyinosine,dideoxycytosine; epinephrine; isoflurphate; adriamycin; bleomycin;mitomycin; ara-C; actinomycin D; scopolamine; and the like, analgesics,such as codeine, morphine, ketorolac, naproxen, an anesthetic,lidocaine; beta.-adrenergic blocker or beta -adrenergic agonist such asephedrine, and epinephrine; aldose reductase inhibitor such asepalrestat, ponalrestat, sorbinil, tolrestat; antiallergic such ascromolyn, beclomethasone, dexamethasone, and flunisolide; colchicine,anihelminthic agents such as ivermectin and suramin sodium; antiamebicagents such as chloroquine and chlortetracycline; and antifungal agentssuch as amphotericin; anti-angiogenesis compounds such as anecortaveacetate; retinoids such as Tazarotene, anti-glaucoma agents such asbrimonidine (Alphagan and Alphagan P), acetozolamide, bimatoprost(Lumigan), timolol, mebefunolol; memantine; alpha-2 adrenergic receptoragonists; 2-methoxyestradiol; anti-neoplastics such as vinblastine,vincristine, interferons; alpha, beta and gamma., antimetabolites suchas folic acid analogs, purine analogs, and pyrimidine analogs;immunosuppressants such as azathyprine, cyclosporine and mizoribine;miotic agents, such as carbachol, mydriatic agents such as atropine,etc., protease inhibitors such as aprotinin, camostat, gabexate,vasodilators such as bradykinin, epidermal growth factor, basicfibroblast growth factor, nerve growth factors, steroidalanti-inflammatory agents such as 21-acetoxypregnenolone, alclometasone,algestone, amcinonide, beclomethasone, betamethasone, budesonide,chloroprednisone, clobetasol, clobetasone, clocortolone, cloprednol,corticosterone, cortisone, cortivazol, deflazacort, desonide,desoximetasone, dexamethasone, diflorasone, diflucortolone,difluprednate, enoxolone, fluazacort, flucloronide, flumethasone,flunisolide, fluocinolone acetonide, fluocinonide, fluocortin butyl,fluocortolone, fluorometholone, fluperolone acetate, fluprednideneacetate, fluprednisolone, flurandrenolide, fluticasone propionate,formocortal, halcinonide, halobetasol propionate, halometasone,halopredone acetate, hydrocortamate, hydrocortisone, loteprednoletabonate, mazipredone, medrysone, meprednisone, methylprednisolone,mometasone furoate, paramethasone, prednicarbate, prednisolone,prednisolone 25-diethylamino-acetate, prednisolone sodium phosphate,prednisone, prednival, prednylidene, rimexolone, tixocortol,triamcinolone, triamcinolone acetonide, triamcinolone benetonide,triamcinolone hexacetonide; vascular endothelial growth factorinhibitors such as bevacizumab, ranibisumab, pegatanib; transforminggrowth factor inhibitors; fibroblast growth factor inhibitors, and anyof their derivatives.

As to particular embodiments of the inventive intraocular implant theactive agent (24) can be dispersed throughout the biocompatiblebiodegradable polymer of the flexible membrane (12) by mixing the activeagent (24) into the melted biodegradable polymer and then solidifyingthe resulting biodegradable polymer by cooling, having the active agent(24) substantially uniformly dispersed throughout. The biodegradablepolymer or mixture of biodegradable polymers can be selected to have amelting point that is below the temperature at which the active agent(24) becomes reactive or degrades. Alternatively, the active agent (24)can be dispersed throughout the biodegradable polymer by solventcasting, in which the biodegradable polymer is dissolved in a solvent,and the active agent (24) dissolved or dispersed in the solution. Thesolvent is then evaporated, leaving the active agent (24) in thepolymeric matrix of the biodegradable material. Solvent casting requiresthat the biodegradable polymer be soluble in organic solvents.Alternatively, the biodegradable intraocular implant (11) can be placedin a solvent having a concentration of the active agent (24) dissolvedand in which the biodegradable intraocular implant swells. Swelling ofthe biodegradable intraocular implant draws in an amount of the activeagent (24). The solvent can then be evaporated leaving the active agent(24) within the flexible membrane (12) of the biodegradable intraocularimplant (12). As to each method of dispersing the active agent (24)through out the biodegradable polymer of the flexible membrane (12),therapeutic levels of active agent (24) can be included in biocompatiblebiodegradable polymer to treat a particular ocular condition. Thebiodegradable polymer usually comprises at least about 10, at leastabout 20, at least about 30, at least about 40, at least about 50, atleast about 60, at least about 70, at least about 80, or at least about90 weight percent of the implant with the balance of the weight beingthe active agent (24) or other non-active agents (37) dispersed in thebiocompatible biodegradable polymer (shown as open stipples in FIGS. 9and 13; however, the non-active agents are not limited to theseparticular embodiments of the flexible membrane (12)).

Other non-active agents (37) may be included in the biocompatiblebiodegradable polymer formulation for a variety of purposes. Forexample, buffering agents and preservatives may be employed.Preservatives which may be used include, but are not limited to, sodiumbisulfate, sodium bisulfate, sodium thiosulfate, benzalkonium chloride,chlorobutanol, thimerosal, phenylmercuric acetate, phenylmercuricnitrate, methylparaben, polyvinyl alcohol and phenylethyl alcohol.Examples of buffering agents that may be employed include, but are notlimited to, sodium carbonate, sodium borate, sodium phosphate, sodiumacetate, sodium bicarbonate, and the like, as approved by the FDA forthe desired route of administration. Electrolytes such as sodiumchloride and potassium chloride may also be included in the formulation.

A non-limiting example of producing biodegradable embodiments theinventive intraocular implant for treating an ocular condition such asPCO can be made by mixing an active agent (24) and biodegradable polymerto form an active agent polymer material. The active agent polymermaterial can be extruded or molded to form embodiments of thebiocompatible biodegradable intraocular implant (11) or flexiblemembrane (12) having active agent release characteristics at atherapeutic level. As but one non-limiting example, the intraocularimplant (11) can substantially continuously release active agent (24) toprovide a localized concentration of alkylphosphocholine at therapeuticlevels of about 0.5 mM to 1.5 mM for at least 5 days or releasemitomycin-C to provide a localized concentration of 0.04 mg/mL, or both,for a period of at least about five days to inhibit or prevent PCO. Itis to be understood that this specific example of providing anembodiment of an intraocular implant (11) for the inhibition orprevention of PCO, is not intended to be limiting, and embodiments ofthe intraocular implant (11) can be utilized to treat a wide range ofocular conditions including posterior ocular conditions or anteriorchamber conditions of the eye.

Embodiments of the biocompatible flexible membrane (12) or thebiocompatible biodegradable flexible membrane (12) can be made by avariety of methods, and while not particularly limited, examples ofmolding methods which can be used to form a film or sheet includes T-diemolding, inflation molding, calender molding, heat press molding, spincast molding, injection molding, cast molding, or the like.

The inventive intraocular implant (11) of a biodegradable polymer of theinvention can be molded in thinner thickness in order to increasebiodegradability, but its thickness can be freely adjusted to satisfystrength, flexibility and release of active agents (24) to achievetherapeutically effective levels localized to the site of implantationof the intraocular implant. Thickness of the flexible membrane can be inthe range of about 5 μm to about 300 μm, or about 10 μm to 100 μm.Elastic modulus of the flexible can generally be 1,200 MPa or less, morepreferably 600 MPa or less. Tensile strength can fall in the range ofabout 10 MPa to 100 MPa, more preferably in a range of 15 MPa to 70 MPa,further more preferably in a range of 20 MPa to 50 MPa.

Again referring primarily to FIGS. 1-4, as above described the mostcommon surgical technique of cataract surgery may be ECCE (although useof the inventive intraocular implant (11) is not limited to cataractsurgery or to any particular technique of cataract surgery) whichinvolves the creation of a circular opening (44) in the anterior lenscapsule (43) through which the opacified lens (3) can be removed. Theremaining portion of the lens capsule (45), anchored to the ciliary body(6) through the zonular fibers (7) can be left intact. The IOL (8) canthen be placed within the lens capsule (45). The IOL (8) can be acted onby zonular forces exerted on the outer circumference of the lens capsule(45) which establishes the location of the IOL (8) within the lenscapsule (45). The intact posterior capsule (5) acts as a barrier to thevitreous humor (9).

Now referring primarily to FIGS. 40 through 42, following cataractextraction and cortex removal by ECCE or other surgical procedures totreat other ocular conditions, embodiments of the biocompatible orbiocompatible biodegradable intraocular implant (11) can be held inforceps (38) as shown for example in FIG. 40. Embodiments of theintraocular implant (11) may also be removably fixed to the surface of asmall card (41)(or intraocular implant packaging substrate) from whichit can be lifted with the forceps (38) prior to insertion into the eyeas shown for example in FIGS. 41 and 42. The intraocular implant (11)can be folded upon itself to reduce the apparent dimension for passagethrough the corneal or scleral incision (42) as well as circular opening(44) in the anterior lens capsule (43) surrounded by the pupil (39) ofthe iris (40), as shown in FIGS. 40-42.

Now referring specifically to FIG. 42, which provides an example of anon-limiting method, the intraocular implant (11) can be positionedwithin localized region of the lens capsule (45) having a front surface(18)(which can further provide patterned surface elements (20) as abovedescribed) proximate the surface or engaging the surface of theposterior capsule (5). The passage opening (33), of embodiments of theintraocular implant (11) which provide an aperture element (32), can bealigned with the visual axis of the eye (21) to provide a line of sightwhich passes through the passage opening (33) of the intraocular implant(11)(or the first annular zone or the second annular zone of theintraocular implant). The IOL (8) can then be located inside the lenscapsule (45) by conventional methods to overlay the intraocular implant(11) placed in the cavity of the posterior capsule (5).

As a non-limiting example, FIG. 43 shows the IOL (8) overlying theintraocular implant (11) with the passage opening (33) of the apertureelement (32) centered underneath the IOL (8). If centration of theintraocular implant (11) is not adequate, it can be readily manipulatedinto position with a Sinskey Hook or similar instrument. Once implantedinto the eye, particular embodiments of the biocompatible biodegradableintraocular implant (12) can biodegrade as above described with normalturnover of the fluid of the eye.

Now referring primarily to FIG. 44, a non-limiting example of anembodiment of the intraocular implant (11) shown in FIGS. 6 and 11having an annular member (74) can be placed in the cavity of theposterior capsule (5) with the edge (80) of the annular member (74)located proximate the perimeter of the sulcus (81) of the lens capsule(45). The IOL (8) can be located in the lens capsule (45) byconventional methods to overlay the intraocular implant (11) with thehaptics (10) engaged with the inside surface (77) of the annular member(74) and the lens of the IOL (8) substantially centered with the visualaxis (21).

Now referring primarily to FIG. 45, a non-limiting example of aone-piece intraocular implant (11) as shown in FIGS. 12 and 13 can beplaced in the cavity of the posterior capsule (5) with the edge (80) ofthe annular member (74) located proximate the sulcus of the lens capsule(45). The one piece IOL (8) can be located in the lens capsule (45) byconventional methods to align the lens of the one piece IOL (8) with thevisual axis (21).

Now referring primarily to FIG. 45, in those surgical procedures inwhich the natural crystalline lens (3) is not removed such as retinalsurgery, cornea transplant surgery, glaucoma surgery, or the like, or incataract surgery in which the intraocular implant (11) is not locatedposterior the IOL (8) (for example, due to posterior capsule tear), theintraocular implant (12) can be placed anterior to the natural lens (3)or the IOL (8) within the ciliary sulcus.

Now referring primarily to FIGS. 47 and 48, the invention can furtherinclude a intraocular implant packaging substrate (41) on whichembodiments of the inventive intraocular implant (11) can be releasablyfixed. The intraocular implant (11) can be removed by manipulation withforceps (38) for use in various applications as above described.

As can be easily understood from the foregoing, the basic concepts ofthe present invention may be embodied in a variety of ways. Theinvention involves numerous and varied embodiments of an intraocularimplant (11) which as to particular embodiments can be used but is notlimited to control of migration of residual lens epithelial cellsbetween the posterior surface of an IOL (8) and the surface of theposterior capsule (5) of the eye to reduce opacification of theposterior capsule (5).

As such, the particular embodiments or elements of the inventiondisclosed by the description or shown in the figures or tablesaccompanying this application including the best mode are not intendedto be limiting, but rather exemplary of the numerous and variedembodiments generically encompassed by the invention or equivalentsencompassed with respect to any particular element thereof. In addition,the specific description of a single embodiment or element of theinvention may not explicitly describe all embodiments or elementspossible; many alternatives are implicitly disclosed by the descriptionand figures.

It should be understood that each element of an apparatus or each stepof a method may be described by an apparatus term or method term. Suchterms can be substituted where desired to make explicit the implicitlybroad coverage to which this invention is entitled. As but one example,it should be understood that all steps of a method may be disclosed asan action, a means for taking that action, or as an element which causesthat action. Similarly, each element of an apparatus may be disclosed asthe physical element or the action which that physical elementfacilitates. As but one example, the disclosure of “an implant” shouldbe understood to encompass disclosure of the act of “implanting”—whetherexplicitly discussed or not—and, conversely, were there effectivelydisclosure of the act of “implanting”, such a disclosure should beunderstood to encompass disclosure of “an implant” and even a “means forimplanting.” Such alternative terms for each element or step are to beunderstood to be explicitly included in the description.

In addition, as to each term used it should be understood that unlessits utilization in this application is inconsistent with suchinterpretation, common dictionary definitions should be understood toincluded in the description for each term as contained in the RandomHouse Webster's Unabridged Dictionary, second edition, each definitionhereby incorporated by reference.

Thus, the applicant(s) should be understood to claim at least: i) eachof the intraocular implants herein disclosed and described, ii) therelated methods disclosed and described, iii) similar, equivalent, andeven implicit variations of each of these devices and methods, iv) thosealternative embodiments which accomplish each of the functions shown,disclosed, or described, v) those alternative designs and methods whichaccomplish each of the functions shown as are implicit to accomplishthat which is disclosed and described, vi) each feature, component, andstep shown as separate and independent inventions, vii) the applicationsenhanced by the various systems or components disclosed, viii) theresulting products produced by such systems or components, ix) methodsand apparatuses substantially as described hereinbefore and withreference to any of the accompanying examples, x) the variouscombinations and permutations of each of the previous elementsdisclosed.

The background section of this patent application provides a statementof the field of endeavor to which the invention pertains. This sectionmay also incorporate or contain paraphrasing of certain United Statespatents, patent applications, publications, or subject matter of theclaimed invention useful in relating information, problems, or concernsabout the state of technology to which the invention is drawn toward. Itis not intended that any United States patent, patent application,publication, statement or other information cited or incorporated hereinbe interpreted, construed or deemed to be admitted as prior art withrespect to the invention.

The claims set forth in this specification, if any, are herebyincorporated by reference as part of this description of the invention,and the applicant expressly reserves the right to use all of or aportion of such incorporated content of such claims as additionaldescription to support any of or all of the claims or any element orcomponent thereof, and the applicant further expressly reserves theright to move any portion of or all of the incorporated content of suchclaims or any element or component thereof from the description into theclaims or vice-versa as necessary to define the matter for whichprotection is sought by this application or by any subsequentapplication or continuation, division, or continuation-in-partapplication thereof, or to obtain any benefit of, reduction in feespursuant to, or to comply with the patent laws, rules, or regulations ofany country or treaty, and such content incorporated by reference shallsurvive during the entire pendency of this application including anysubsequent continuation, division, or continuation-in-part applicationthereof or any reissue or extension thereon.

The claims set forth in this specification, if any, are further intendedto describe the metes and bounds of a limited number of the preferredembodiments of the invention and are not to be construed as the broadestembodiment of the invention or a complete listing of embodiments of theinvention that may be claimed. The applicant does not waive any right todevelop further claims based upon the description set forth above as apart of any continuation, division, or continuation-in-part, or similarapplication.

1. An intraocular implant comprising: an intraocular lens comprising: anintraocular lens haptic; an intraocular lens optic; where theintraocular lens optic comprises: a biocompatible flexible membranehaving flat front and back surfaces disposed a uniform thickness apart;the biocompatible membrane comprising: an aperture; and a lens; wherethe aperture contacts the lens at an aperture inner diameter of 1.5 to 9millimeters.
 2. The intraocular implant of claim 1, further comprisingan annular member coupled to the front surface of the biocompatibleflexible membrane, the annular member having an edge which defines theouter boundary of the intraocular implant.
 3. The intraocular implant ofclaim 1, wherein the edge has an external surface which intersects withthe back surface of the biocompatible flexible membrane at an anglewhich produces a corner sufficiently sharp to prevent or inhibitmigration of cells toward the center of the intraocular implant.
 4. Theintraocular implant of claim 1, further comprising patterned surfaceelements coupled to the back surface of said biocompatible flexiblemembrane.